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Clinical Trial Results:
A Phase 1/2a Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AFM24 in Combination with Atezolizumab in Patients with Selected Advanced/Metastatic EGFR-expressing Cancers

Summary
EudraCT number	2021-000707-20
Trial protocol	ES PL
Global end of trial date	11 Jun 2025

Results information
Results version number	v1(current)
This version publication date	06 Aug 2025
First version publication date	06 Aug 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

AFM24-102

ISRCTN number

US NCT number

NCT05109442

WHO universal trial number (UTN)

Sponsor organisation name

Affimed GmbH

Sponsor organisation address

Gottlieb-Daimler-Straße 2, Mannheim, Germany, 68165

Public contact

Clinical Trial Manager, Affimed GmbH, +49 6221 6743-621, u.gaertner@affimed.com

Scientific contact

Clinical Trial Manager, Affimed GmbH, +49 6221 6743-621, u.gaertner@affimed.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

07 Apr 2025

Is this the analysis of the primary completion data?

Yes

Primary completion date

06 Mar 2025

Global end of trial reached?

Yes

Global end of trial date

11 Jun 2025

Was the trial ended prematurely?

Yes

Main objective of the trial

Dose Escalation Phase (Phase 1): -To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AFM24 in combination with atezolizumab. Phase 2a: -To evaluate the antitumor activity of AFM24 in combination with atezolizumab in terms of ORR.

Protection of trial subjects

Subjects were considered eligible to be enrolled in the study only if all of the inclusion and none of the exclusion criteria were met. Subjects were qualified to receive the investigational treatment only if they were deemed eligible post the Safety Lead-in phase where they received a single i.v. AFM24 infusion on Day-7, and were then observed for any AE for 1 week.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Aug 2021

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

20 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 23

Country: Number of subjects enrolled

Spain: 42

Country: Number of subjects enrolled

United Kingdom: 7

Country: Number of subjects enrolled

United States: 5

Country: Number of subjects enrolled

Korea, Republic of: 35

Worldwide total number of subjects

112

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was an interventional, Phase 1/2a, Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AFM24 in Combination with Atezolizumab in subjects with documented histologically or cytologically confirmed select advanced or metastatic EGFR-positive cancers.

Screening details

EXP-2 and EXP-3 subjects were pre-screened to assess EGFR expression. All subjects attended screening assessments that included review of subject’s medical history, assessment of ECOG performance status, physical examination, ECG, laboratory assessments, tumor assessments and histopathology. Population of trial tables are based on the Safety set.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

AFM24 160 mg + atezolizumab 840 mg

Arm description

Subjects with confirmed selected advanced or metastatic epidermal growth factor receptor (EGFR)-positive cancers were administered one dose of 160 milligram (mg) AFM24 once weekly via intravenous (i.v.) infusion. Approximately 1 hour before AFM24 infusion, subjects were required to receive the following premedications: dexamethasone, H1 antagonist and optionally a H2 antagonist, and acetaminophen. Subjects were also administered one dose of 840 mg atezolizumab once every two weeks via i.v. infusion. Subjects could receive the investigational treatment in recurring 4-week cycles until disease progression, intolerable toxicity, investigator discretion, or subject's withdrawal of consent, whichever occurred first. Subjects received treatment only if they did not have a Grade ≥3 cytokine release syndrome (CRS) or infusion-related reaction (IRR) or any other possible related Grade ≥3 treatment-emergent adverse events (TEAEs) after 1 dose of AFM24 (Safety Lead-in phase, Day -7 to Day -1).

Arm type

Experimental

Investigational medicinal product name

AFM24

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 160 mg administered once weekly.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 840 mg once every two weeks.

AFM24 480 mg + atezolizumab 840 mg

Arm description

Subjects with confirmed selected advanced or metastatic EGFR-positive cancers were administered one dose of 480 mg AFM24 once weekly via i.v. infusion. Approximately 1 hour before AFM24 infusion, subjects were required to receive the following premedications: dexamethasone, H1 antagonist and optionally a H2 antagonist, and acetaminophen. Subjects were also administered one dose of 840 mg atezolizumab once every two weeks via i.v. infusion. Subjects could receive the investigational treatment in recurring 4-week cycles until disease progression, intolerable toxicity, investigator discretion, or subject's withdrawal of consent, whichever occurred first. Subjects received treatment only if they did not have a Grade ≥3 CRS or IRR or any other possible related Grade ≥3 TEAEs after 1 dose of AFM24 (Safety Lead-in phase, Day -7 to Day -1).

Arm type

Experimental

Investigational medicinal product name

AFM24

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 480 mg administered once weekly.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 840 mg once every two weeks.

EXP-1: EGFR-WT NSCLC

Arm description

Subjects with metastatic EGFR-wild type (EGFR-wt)-expressing non-small cell lung cancer (NSCLC) were administered one dose of 480 mg AFM24 once weekly via i.v. infusion. Approximately 1 hour before AFM24 infusion, subjects were required to receive the following premedications: dexamethasone, H1 antagonist and optionally a H2 antagonist, and acetaminophen. Subjects were also administered one dose of 840 mg atezolizumab once every two weeks via i.v. infusion. Subjects were treated in recurring 4-week cycles until disease progression, intolerable toxicity, death, or discontinuation from the study, whichever occurred first. Subjects received treatment only if they did not have a Grade ≥3 CRS or IRR or any other possible related Grade ≥3 TEAEs after 1 dose of AFM24 (Safety Lead-in phase, Day -7 to Day -1).

Arm type

Experimental

Investigational medicinal product name

AFM24

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 480 mg administered once weekly.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 840 mg once every two weeks.

EXP-2: Gastric or GEJ adenocarcinoma

Arm description

Subjects with locally advanced, unresectable, or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma were administered one dose of 480 mg AFM24 once weekly via i.v. infusion. Approximately 1 hour before AFM24 infusion, subjects were required to receive the following premedications: dexamethasone, H1 antagonist and optionally a H2 antagonist, and acetaminophen. Subjects were also administered one dose of 840 mg atezolizumab once every two weeks via i.v. infusion. Subjects were treated in recurring 4-week cycles until disease progression, intolerable toxicity, death, or discontinuation from the study, whichever occurred first. Subjects received treatment only if they did not have a Grade ≥3 CRS or IRR or any other possible related Grade ≥3 TEAEs after 1 dose of AFM24 (Safety Lead-in phase, Day -7 to Day -1).

Arm type

Experimental

Investigational medicinal product name

AFM24

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 480 mg administered once weekly.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 840 mg once every two weeks.

EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma

Arm description

Subjects with advanced or metastatic hepatocellular carcinoma (other than fibrolamellar and sarcomatoid subtype, Barcelona Clinic Liver Cancer Stage C disease or Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy), hepatobiliary or pancreatic adenocarcinoma, were administered one dose of 480 mg AFM24 once weekly via i.v. infusion. Approximately 1 hour before AFM24 infusion, subjects were required to receive the following premedications: dexamethasone, H1 antagonist and optionally a H2 antagonist, and acetaminophen. Subjects were also administered one dose of 840 mg atezolizumab once every two weeks via i.v. infusion. Subjects were treated in recurring 4-week cycles until disease progression, intolerable toxicity, death, or discontinuation from the study, whichever occurred first. Subjects received treatment only if they did not have a Grade ≥3 CRS or IRR or any other possible related Grade ≥3 TEAEs in the Safety Lead-in phase (Day -7 to Day -1).

Arm type

Experimental

Investigational medicinal product name

AFM24

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 480 mg administered once weekly.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 840 mg once every two weeks.

EXP-4: EGFR mutated NSCLC

Arm description

Subjects with advanced or metastatic NSCLC harboring a targetable EGFR kinase domain mutation were administered one dose of 480 mg AFM24 once weekly via i.v. infusion. Approximately 1 hour before AFM24 infusion, subjects were required to receive the following premedications: dexamethasone, H1 antagonist and optionally a H2 antagonist, and acetaminophen. Subjects were also administered one dose of 840 mg atezolizumab once every two weeks via i.v. infusion. Subjects were treated in recurring 4-week cycles until disease progression, intolerable toxicity, death, or discontinuation from the study, whichever occurred first. Subjects received treatment only if they did not have a Grade ≥3 CRS or IRR or any other possible related Grade ≥3 TEAEs after 1 dose of AFM24 (Safety Lead-in phase, Day -7 to Day -1).

Arm type

Experimental

Investigational medicinal product name

AFM24

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 480 mg administered once weekly.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

One dose of 840 mg once every two weeks.

Number of subjects in period 1	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Started	4	6	49	12	11	30
Completed	0	0	0	0	0	0
Not completed	4	6	49	12	11	30
Consent withdrawn by subject	-	-	1	-	-	-
Adverse event, non-fatal	-	1	5	-	-	2
Death	-	-	4	-	-	1
Investigator’s decision	1	-	1	-	-	2
Other than listed	-	-	9	2	-	8
Disease Progression	3	5	29	10	11	17

Baseline characteristics

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Reporting group title

AFM24 160 mg + atezolizumab 840 mg

Reporting group description

Reporting group title

AFM24 480 mg + atezolizumab 840 mg

Reporting group description

Reporting group title

EXP-1: EGFR-WT NSCLC

Reporting group description

Reporting group title

EXP-2: Gastric or GEJ adenocarcinoma

Reporting group description

Reporting group title

EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma

Reporting group description

Reporting group title

EXP-4: EGFR mutated NSCLC

Reporting group description

Reporting group values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC	Total
Number of subjects	4	6	49	12	11	30	112
Age categorical
Safety Analysis Set: all subjects who received at least any amount of AFM24 or atezolizumab.
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	2	3	16	10	7	14	52
From 65-84 years	2	3	33	2	4	16	60
85 years and over	0	0	0	0	0	0	0
Age continuous
Safety Analysis Set: all subjects who received at least any amount of AFM24 or atezolizumab.
Units: years
arithmetic mean (standard deviation)	60.8 ( 10.28 )	55.0 ( 20.24 )	64.9 ( 9.1 )	59.2 ( 7.5 )	58.3 ( 12.1 )	64.2 ( 9.5 )	-
Gender categorical
Safety Analysis Set: all subjects who received at least any amount of AFM24 or atezolizumab.
Units: Subjects
Female	4	4	13	3	7	20	51
Male	0	2	36	9	4	10	61
Race (NIH/OMB)
Safety Analysis Set: all subjects who received at least any amount of AFM24 or atezolizumab.
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	0	0	18	0	1	18	37
Black or African American	0	0	1	0	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
White	4	6	30	12	9	12	73
Unknown or Not Reported	0	0	0	0	1	0	1
Other	0	0	0	0	0	0	0
Ethnicity (NIH/OMB)
Safety Analysis Set: all subjects who received at least any amount of AFM24 or atezolizumab.
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	0
Not Hispanic or Latino	4	6	45	12	10	30	107
Unknown or Not Reported	0	0	4	0	1	0	5

End points

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Reporting group title

AFM24 160 mg + atezolizumab 840 mg

Reporting group description

Reporting group title

AFM24 480 mg + atezolizumab 840 mg

Reporting group description

Reporting group title

EXP-1: EGFR-WT NSCLC

Reporting group description

Reporting group title

EXP-2: Gastric or GEJ adenocarcinoma

Reporting group description

Reporting group title

EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma

Reporting group description

Reporting group title

EXP-4: EGFR mutated NSCLC

Reporting group description

Primary: Phase 1 - Adverse events to be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period (Cycle 1)

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End point title

Phase 1 - Adverse events to be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period (Cycle 1) ^[1] ^[2]

End point description

A DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to underlying disease, disease progression, inter-current illness, or concomitant medications, that occurs ≤28 days following the first dose of AFM24 in combination with atezolizumab and that meets any of the following criteria: ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 4 neutropenia lasting for longer than 4 consecutive days; febrile neutropenia that does not resolve within 48 hours after start of antibiotics; CTCAE Grade 3 (associated with bleeding) or Grade 4 thrombocytopenia; ≥CTCAE Grade 4 anemia considered to be treatment related; any death at least possibly related to any study drug; any ≥CTCAE Grade 3 AE. Exceptions to the DLT criteria may apply. Dose-Determining Set (DDS): all subjects in the SAS who experienced DLT or met the minimum safety evaluation requirements without experiencing DLT during Cycle 1.

End point type

Primary

End point timeframe

From first drug administration, until the end of the end of the Cycle 1, up to 28 days.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: According to the Protocol, the endpoint was only analyzed descriptively.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: According to the Protocol, the endpoint only considers subjects in the Phase 1.

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg
Number of subjects analysed	4	6
Units: Count of subjects	0	1

No statistical analyses for this end point

Primary: Phase 2a - Objective response rate according to RECIST v1.1 determined by Investigator assessment

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End point title

Phase 2a - Objective response rate according to RECIST v1.1 determined by Investigator assessment ^[3] ^[4]

End point description

Objective response rate (ORR) according to Response Evaluate Criteria in Solid Tumors (RECIST) v1.1 determined by Investigator assessment is reported as the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST v1.1 criteria. RECIST v1.1 for target lesions and assessed by computed tomography (CT) or (magnetic resonance imaging) MRI: CR, Disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions; Overall Response = CR + PR. Full Analysis Set (FAS): all subjects who completed the Safety Lead-In phase and received any amount of any component of the combination treatments AFM24 and atezolizumab.

End point type

Primary

End point timeframe

On Day 22 of Cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter, up to approximately 97 weeks.

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: According to the Protocol, the endpoint was only analyzed descriptively.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: According to the Protocol, the endpoint only considers subjects in the Phase 2a.

End point values	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	43	12	11	28
Units: Count of subjects	8	1	1	4

No statistical analyses for this end point

Secondary: Phase 1 - Objective response rate according to RECIST v1.1 determined by Investigator assessment

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End point title

Phase 1 - Objective response rate according to RECIST v1.1 determined by Investigator assessment ^[5]

End point description

End point type

Secondary

End point timeframe

On Day 22 of Cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter, up to 27 weeks.

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: According to the Protocol, the endpoint only considers subjects in the Phase 1.

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg
Number of subjects analysed	3	6
Units: Count of subjects	1	0

No statistical analyses for this end point

Secondary: Phase 2a - Progression-Free Survival according to RECIST v1.1 by Investigator assessment

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End point title

Phase 2a - Progression-Free Survival according to RECIST v1.1 by Investigator assessment ^[6]

End point description

Progression-Free Survival (PFS) was determined as follows: (date of first progression or death [in the absence of progression] – date of first study drug injection)/30.4375. Subjects without progression or death were censored. Progression was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable unequivocal increase in a non-target lesion, or the appearance of new lesion. Full Analysis Set (FAS): all subjects who completed the Safety Lead-In phase and received any amount of any component of the combination treatments AFM24 and atezolizumab.

End point type

Secondary

End point timeframe

From Cycle 1 Day 1 until the date of disease progression or death from any cause, whichever occurs first, up to approximately 97 weeks.

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: According to the Protocol, the endpoint only considers subjects in the Phase 2a.

End point values	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	43	12	11	28
Units: Month
median (confidence interval 95%)	3.7454 (1.9055 to 5.848)	1.9384 (1.4784 to 8.7064)	1.9055 (0.9856 to 2.5298)	3.7125 (1.8727 to 7.4579)

No statistical analyses for this end point

Secondary: Phase 2a - Duration of Response according to RECIST v1.1 by Investigator assessment

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End point title

Phase 2a - Duration of Response according to RECIST v1.1 by Investigator assessment ^[7]

End point description

Duration of Response (DOR) was measured as follows: (date of first progression or death – date of first response [unconfirmed])/30.4375. Subjects without response were excluded from the analysis. Subjects without progression or death were censored. Response criteria (CR or PR) were defined using RECIST v1.1. Full Analysis Set (FAS): all subjects who completed the Safety Lead-In phase and received any amount of any component of the combination treatments AFM24 and atezolizumab. 9999 = Not enough events to calculate the data.

End point type

Secondary

End point timeframe

From date of first response until progression or death, up to approximately 97 weeks.

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: According to the Protocol, the endpoint only considers subjects in the Phase 2a.

End point values	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	8	1	1	4
Units: Month
median (confidence interval 95%)	9.20 (3.71 to 9999)	9999 (9999 to 9999)	3.71 (-9999 to 9999)	11.07 (6.54 to 9999)

No statistical analyses for this end point

Secondary: Phase 2a - Clinical benefit rate according to RECIST v1.1 by Investigator assessment

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End point title

Phase 2a - Clinical benefit rate according to RECIST v1.1 by Investigator assessment ^[8]

End point description

Clinical benefit rate (CBR) was measured per RECIST v1.1 criteria as the number of subjects who achieved overall tumor response (CR or PR) of any duration, or Stable Disease (SD) for at least 24 weeks. Full Analysis Set (FAS): all subjects who completed the Safety Lead-In phase and received any amount of any component of the combination treatments AFM24 and atezolizumab.

End point type

Secondary

End point timeframe

On Day 22 of Cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter, up to approximately 97 weeks.

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: According to the Protocol, the endpoint only considers subjects in the Phase 2a.

End point values	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	43	12	11	28
Units: Count of subjects	11	2	1	8

No statistical analyses for this end point

Secondary: Phase 2a - Disease control rate according to RECIST v1.1 by Investigator assessment

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End point title

Phase 2a - Disease control rate according to RECIST v1.1 by Investigator assessment ^[9]

End point description

Disease control rate (DCR) was defined by achieving CR and/or PR and/or SD assessed by RECIST v1.1. Full Analysis Set (FAS): all subjects who completed the Safety Lead-In phase and received any amount of any component of the combination treatments AFM24 and atezolizumab.

End point type

Secondary

End point timeframe

On Day 22 of Cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter, up to approximately 97 weeks.

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: According to the Protocol, the endpoint only considers subjects in the Phase 2a.

End point values	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	43	12	11	28
Units: Count of subjects	27	5	2	14

No statistical analyses for this end point

Secondary: Number of patients with Treatment-Emergent Adverse Events and Serious Adverse Events

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End point title

Number of patients with Treatment-Emergent Adverse Events and Serious Adverse Events

End point description

Number of patients with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) is reported on the safety Analysis Set (all subjects who received at least any amount of AFM24 or atezolizumab).

End point type

Secondary

End point timeframe

From first drug administration up to 30 (TEAEs) or 56 (SAEs) days after the last dose of AFM24, until the start of a subsequent anticancer treatment, or data cut-off date, whichever is sooner. Up to approximately 35 (phase 1) and 100 weeks (phase 2a).

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	4	6	49	12	11	30
Units: Count of subjects
Treatment-Emergent Adverse Events	4	6	49	11	11	30
Serious Adverse Events	2	3	30	6	7	15

No statistical analyses for this end point

Secondary: Maximum concentration of AFM24 over the dosing interval (Cmax)

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End point title

Maximum concentration of AFM24 over the dosing interval (Cmax)

End point description

Maximum concentration of AFM24 over the dosing interval (Cmax) in Cycle 1 is reported based on the Pharmacokinetics (PK) set (all subjects who have received at least 1 adequately documented dose of AFM24 and have at least 1 adequately documented post dose PK measurement). Only subjects with available PK data are included in the analysis.

End point type

Secondary

End point timeframe

Within 2 hours (h) prior to 1st drug infusion, at the end of first AFM24 infusion, 48 h and 144 h (Phase 1 only) after the end of first AFM24 infusion, within 2 h prior to the 2nd, 3rd and 4th drug infusion, and at the of the fourth AFM24 infusion.

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	3	4	35	11	8	20
Units: nanogram/milliliter
arithmetic mean (standard deviation)	73700 ( 25400 )	269000 ( 61400 )	207000 ( 78100 )	207000 ( 73400 )	175000 ( 77200 )	250000 ( 106000 )

No statistical analyses for this end point

Secondary: Time to maximum concentration of AFM24 over the dosing interval (Tmax)

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End point title

Time to maximum concentration of AFM24 over the dosing interval (Tmax)

End point description

Time to maximum concentration of AFM24 over the dosing interval (Tmax) in Cycle 1 is reported based on the Pharmacokinetics (PK) set (all subjects who have received at least 1 adequately documented dose of AFM24 and have at least 1 adequately documented post dose PK measurement). Only subjects with available PK data are included in the analysis.

End point type

Secondary

End point timeframe

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	3	4	35	11	8	20
Units: Hour (h)
arithmetic mean (standard deviation)	3.15 ( 0.03 )	3.15 ( 0.13 )	9.78 ( 17.9 )	27.9 ( 24.5 )	8.63 ( 15.8 )	10.6 ( 17.4 )

No statistical analyses for this end point

Secondary: Minimum concentration of AFM24 over the dosing interval (Cmin)

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End point title

Minimum concentration of AFM24 over the dosing interval (Cmin)

End point description

Minimum concentration of AFM24 over the dosing interval (Cmin), corresponding to trough concentration (Ctrough) levels at the end of the dosing interval, in Cycle 1 is reported based on the Pharmacokinetics (PK) set (all subjects who have received at least 1 adequately documented dose of AFM24 and have at least 1 adequately documented post dose PK measurement). Only subjects with available PK data are included in the analysis.

End point type

Secondary

End point timeframe

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	3	4	36	12	7	19
Units: nanogram/milliliter
arithmetic mean (standard deviation)	16700 ( 12500 )	105000 ( 37200 )	56300 ( 48500 )	73700 ( 40900 )	71900 ( 62500 )	93700 ( 51600 )

No statistical analyses for this end point

Secondary: The area under the curve (AUC) of AFM24 from the time of dosing to 168 hours post dose (AUCtau)

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End point title

The area under the curve (AUC) of AFM24 from the time of dosing to 168 hours post dose (AUCtau)

End point description

The area under the curve (AUC) of AFM24 from the time of dosing to 168 hours post dose (AUCtau) in Cycle 1 is reported based on the Pharmacokinetics (PK) set (all subjects who have received at least 1 adequately documented dose of AFM24 and have at least 1 adequately documented post dose PK measurement). Only subjects with available PK data are included in the analysis.

End point type

Secondary

End point timeframe

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	3	3	31	11	7	15
Units: microgram*hour/milliliter
arithmetic mean (standard deviation)	5760 ( 919 )	27900 ( 9780 )	19800 ( 9660 )	21500 ( 8620 )	20500 ( 11400 )	28600 ( 11900 )

No statistical analyses for this end point

Secondary: Number of patients developing antidrug antibodies against AFM24

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End point title

Number of patients developing antidrug antibodies against AFM24

End point description

Number of patients developing antidrug antibodies (ADAs) against AFM24 is reported on the safety Analysis Set (all subjects who received at least any amount of AFM24 or atezolizumab).

End point type

Secondary

End point timeframe

Phase 1: within 2h prior to each drug intake (Cycle 1), within 2 h prior to 1st and 3rd drug intake (Cycle 2 onwards) and at the End of Treatment (EOT), up to 27 weeks. Phase 2a: within 2h prior to 1st drug intake (each Cycle) and EOT, up to 97 weeks.

End point values	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Number of subjects analysed	4	6	49	12	11	30
Units: Count of subjects	1	2	12	2	3	7

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse event reporting additional description

Safety Analysis Set: all subjects who received at least any amount of AFM24 or atezolizumab. Deaths were collected until the end of the study, up to approximately 100 weeks.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

AFM24 160 mg + atezolizumab 840 mg

Reporting group description

Reporting group title

AFM24 480 mg + atezolizumab 840 mg

Reporting group description

Reporting group title

EXP-1: EGFR-WT NSCLC

Reporting group description

Reporting group title

EXP-2: Gastric or GEJ adenocarcinoma

Reporting group description

Reporting group title

EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma

Reporting group description

Reporting group title

EXP-4: EGFR mutated NSCLC

Reporting group description

Serious adverse events	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 4 (50.00%)	3 / 6 (50.00%)	30 / 49 (61.22%)	6 / 12 (50.00%)	7 / 11 (63.64%)	15 / 30 (50.00%)
number of deaths (all causes)	3	5	21	9	9	9
number of deaths resulting from adverse events	0	0	5	0	1	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cancer pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Vascular disorders
Pelvic venous thrombosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Superior vena cava syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 49 (2.04%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthermia malignant
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	3 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Vaginal prolapse
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	4 / 49 (8.16%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 5	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Sputum increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Organising pneumonia
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood bilirubin increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	1 / 12 (8.33%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	3 / 4	1 / 1	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac tamponade
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia of malignant disease
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Dysphagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	2 / 12 (16.67%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Jaundice cholestatic
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	5 / 49 (10.20%)	1 / 12 (8.33%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 6	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Biliary sepsis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Escherichia bacteraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyponatraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypophagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	AFM24 160 mg + atezolizumab 840 mg	AFM24 480 mg + atezolizumab 840 mg	EXP-1: EGFR-WT NSCLC	EXP-2: Gastric or GEJ adenocarcinoma	EXP-3: Carcinoma, Hepatobiliary or Pancreatic Adenocarcinoma	EXP-4: EGFR mutated NSCLC
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	6 / 6 (100.00%)	48 / 49 (97.96%)	11 / 12 (91.67%)	11 / 11 (100.00%)	29 / 30 (96.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	3	0	0	2
Cancer pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	4	0	1	0
Vascular disorders
Haematoma
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	1	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	7 / 49 (14.29%)	5 / 12 (41.67%)	8 / 11 (72.73%)	5 / 30 (16.67%)
occurrences all number	1	1	9	9	13	6
Fatigue
subjects affected / exposed	0 / 4 (0.00%)	2 / 6 (33.33%)	8 / 49 (16.33%)	1 / 12 (8.33%)	0 / 11 (0.00%)	4 / 30 (13.33%)
occurrences all number	0	2	9	1	0	4
Pyrexia
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	5 / 49 (10.20%)	1 / 12 (8.33%)	2 / 11 (18.18%)	3 / 30 (10.00%)
occurrences all number	1	1	5	1	3	3
Chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	2	1	0	0
Chills
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 49 (2.04%)	0 / 12 (0.00%)	2 / 11 (18.18%)	0 / 30 (0.00%)
occurrences all number	0	1	1	0	2	0
Oedema peripheral
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	2 / 12 (16.67%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	2	1	0
Malaise
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	0	1	0	0
Swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	5 / 49 (10.20%)	0 / 12 (0.00%)	0 / 11 (0.00%)	5 / 30 (16.67%)
occurrences all number	1	1	6	0	0	5
Dyspnoea
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	4 / 49 (8.16%)	1 / 12 (8.33%)	1 / 11 (9.09%)	3 / 30 (10.00%)
occurrences all number	1	1	5	1	1	3
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	4	0	0	0
Catarrh
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	0	1	0	0
Dysphonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	1 / 12 (8.33%)	1 / 11 (9.09%)	3 / 30 (10.00%)
occurrences all number	0	0	1	1	1	3
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 4 (25.00%)	3 / 6 (50.00%)	10 / 49 (20.41%)	3 / 12 (25.00%)	0 / 11 (0.00%)	6 / 30 (20.00%)
occurrences all number	2	5	15	6	0	15
Aspartate aminotransferase increased
subjects affected / exposed	1 / 4 (25.00%)	3 / 6 (50.00%)	8 / 49 (16.33%)	3 / 12 (25.00%)	1 / 11 (9.09%)	6 / 30 (20.00%)
occurrences all number	1	3	12	6	2	25
Neutrophil count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	5 / 30 (16.67%)
occurrences all number	0	0	2	0	0	13
Amylase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	4	0	0	4
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)
occurrences all number	0	0	2	0	0	6
Lipase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	0	4	0	0	3
Weight decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	3 / 49 (6.12%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1	4	0	0	2
Bilirubin conjugated increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	2	0
Blood bilirubin increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	1	0	0	0	3	0
Lymphocyte count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	3	0
Waist circumference increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
White blood cells urine positive
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Heart rate decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	1	0	0	0	0
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	2 / 4 (50.00%)	5 / 6 (83.33%)	25 / 49 (51.02%)	9 / 12 (75.00%)	8 / 11 (72.73%)	19 / 30 (63.33%)
occurrences all number	3	6	31	11	9	20
Medication error
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	1	0	2	0	1	0
Procedural pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Radiation mucositis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Tendon rupture
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	4 / 49 (8.16%)	0 / 12 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	11	0	0	2
Paraesthesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	1 / 11 (9.09%)	3 / 30 (10.00%)
occurrences all number	0	0	12	0	1	3
Dizziness
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	1	0	0	2
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	2 / 4 (50.00%)	1 / 6 (16.67%)	4 / 49 (8.16%)	1 / 12 (8.33%)	0 / 11 (0.00%)	5 / 30 (16.67%)
occurrences all number	6	3	8	16	0	8
Anaemia
subjects affected / exposed	2 / 4 (50.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	1 / 12 (8.33%)	3 / 11 (27.27%)	2 / 30 (6.67%)
occurrences all number	5	0	3	8	5	2
Lymphopenia
subjects affected / exposed	3 / 4 (75.00%)	2 / 6 (33.33%)	3 / 49 (6.12%)	0 / 12 (0.00%)	2 / 11 (18.18%)	0 / 30 (0.00%)
occurrences all number	25	3	4	0	4	0
Leukopenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	2 / 11 (18.18%)	1 / 30 (3.33%)
occurrences all number	0	0	0	0	2	1
Thrombocytopenia
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	2 / 11 (18.18%)	0 / 30 (0.00%)
occurrences all number	3	0	0	0	2	0
Increased tendency to bruise
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	2	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	3 / 12 (25.00%)	5 / 11 (45.45%)	3 / 30 (10.00%)
occurrences all number	0	0	6	4	7	3
Constipation
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 49 (4.08%)	1 / 12 (8.33%)	2 / 11 (18.18%)	4 / 30 (13.33%)
occurrences all number	0	1	3	1	3	4
Nausea
subjects affected / exposed	0 / 4 (0.00%)	3 / 6 (50.00%)	5 / 49 (10.20%)	1 / 12 (8.33%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	5	8	1	1	0
Dyspepsia
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	3 / 49 (6.12%)	0 / 12 (0.00%)	2 / 11 (18.18%)	1 / 30 (3.33%)
occurrences all number	0	1	3	0	2	1
Abdominal pain
subjects affected / exposed	0 / 4 (0.00%)	2 / 6 (33.33%)	2 / 49 (4.08%)	1 / 12 (8.33%)	1 / 11 (9.09%)	1 / 30 (3.33%)
occurrences all number	0	2	2	1	1	1
Vomiting
subjects affected / exposed	0 / 4 (0.00%)	2 / 6 (33.33%)	1 / 49 (2.04%)	1 / 12 (8.33%)	2 / 11 (18.18%)	1 / 30 (3.33%)
occurrences all number	0	2	1	1	3	1
Ascites
subjects affected / exposed	3 / 4 (75.00%)	2 / 6 (33.33%)	0 / 49 (0.00%)	2 / 12 (16.67%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	8	3	0	4	1	0
Dry mouth
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	1	0	1	0
Abdominal pain upper
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	0	1	0	0
Dysphagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	0	1	0	0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	0	1	0	0
Hepatobiliary disorders
Jaundice
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Jaundice cholestatic
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	3 / 49 (6.12%)	0 / 12 (0.00%)	2 / 11 (18.18%)	3 / 30 (10.00%)
occurrences all number	0	2	3	0	2	3
Rash
subjects affected / exposed	0 / 4 (0.00%)	2 / 6 (33.33%)	3 / 49 (6.12%)	2 / 12 (16.67%)	1 / 11 (9.09%)	2 / 30 (6.67%)
occurrences all number	0	2	4	2	1	2
Dermatitis acneiform
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	2	0	1	0
Nail disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	1	0	2	0
Acne
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Perioral dermatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	2	0
Rash erythematous
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	1	1	0	0	0
Skin maceration
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 49 (4.08%)	0 / 12 (0.00%)	4 / 11 (36.36%)	4 / 30 (13.33%)
occurrences all number	0	1	2	0	4	5
Arthralgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	4 / 49 (8.16%)	0 / 12 (0.00%)	1 / 11 (9.09%)	2 / 30 (6.67%)
occurrences all number	0	0	7	0	10	2
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	2	0	0	2
Myalgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	0	0	1	0	1
Muscular weakness
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)
occurrences all number	0	0	3	0	0	3
Herpes zoster
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	0 / 12 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)
occurrences all number	0	0	2	0	0	4
Rash pustular
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	5	0	2	0
COVID-19
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 49 (2.04%)	1 / 12 (8.33%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	0	1	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	0	0	0	3
Viral infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	0	0	1	0	1
Otitis media
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	0	0	1	0
Sinusitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1	0	0	0	1
Candida infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 49 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)
occurrences all number	0	1	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 4 (25.00%)	2 / 6 (33.33%)	4 / 49 (8.16%)	1 / 12 (8.33%)	4 / 11 (36.36%)	3 / 30 (10.00%)
occurrences all number	2	3	7	1	4	3
Hyperkalaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	4 / 49 (8.16%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	0	5	0	0	5
Hypocalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)
occurrences all number	0	0	3	0	0	3
Hyponatraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	4 / 49 (8.16%)	0 / 12 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	0	5	0	0	2
Diabetes mellitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 49 (6.12%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	3	0	1	0
Hypokalaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	0	2	0	2
Hypophosphataemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 49 (4.08%)	0 / 12 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)
occurrences all number	0	0	4	0	1	0
Hyperglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 49 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	0	0	2	0	1

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Were there any global substantial amendments to the protocol? Yes

17 May 2021

The overall rationale for this amendment is to correct a typographical error in the page footer.

28 Feb 2022

The following main changes were implemented: update of Medical Monitor contact information following change in personnel; clarification that one or more recommended phase 2 doses (RP2Ds) may be selected; removal of Response Assessment in Neuro-Oncology criteria; clarification of requirement for pre-screening to determine eligibility by EGFR testing; clarification on the conduct and design of Phase 1; specification of the starting dose for the study based on information from the ongoing AFM24-101 study; clarification that that if any of the stopping rules applicable to the expansion phase is met, enrolment in Phase 2a can restart only after approval of a substantial amendment by the regulatory authority; EXP-4 will no longer be included for enrollment in this study and was removed globally; clarification on COVID-19 vaccinations policy; update to exclusion and inclusion criteria; clarification of premedication requirements and addition of pre-medication guidance for split-day dosing; clarification of AFM24 administration details; addition of most current half-life information for AFM24; clarification on pre-screening; revision that survival status should be collected until withdrawal of consent, death, or the end of the study; clarification of instructions for dose interruptions, delays, modification and discontinuations for AFM24 treatment; clarification of the drugs that are prohibited from use during the study; alignment of guidance for management of atezolizumab-related toxicities based on the current Summary of Product Characteristics; updates to the guidance on management of AEs and drug dose modification or discontinuation; clarification of timing and instructions for AE collection; clarification the method and timing for reporting of Serious AEs and AE of Special Interest; changes to the schedule of assessments; addition of laboratory tests.

10 May 2023

The following main changes were implemented: update of study centers; addition of DCR as a secondary endpoint; addition of EXP-4; addition of the involvement of an IDMC to monitor safety throughout Phase 2a; update to inclusion and exclusion criteria; modification of the definition of AFM24 infusions being well tolerated from no IRR/cytokine release syndrome (CRS) Grade >1 to no IRR/CRS Grade >2; clarification on interim analyses performed during the trial; revision of indication for atezolizumab according to the updated Prescribing Information (USPI); inclusion of results from AFM24-101; addition of the rationale for selection of the monotherapy AFM24 RP2D from AFM24-101 study; clarification of the duration of Phase 2a; clarification of study procedures timepoints; addition of optional biopsies for confirmation of disease response/progression and could also be utilized for analysis of immunological and other effects of the drugs on the tumor microenvironment; streamlined safety management section to align and for consistency with Sponsor’s other programs; clarification of timing for collection of AEs and Serious AEs; update to laboratory tests.

09 Dec 2024

The following main changes were implemented: addition of three new expansion cohorts to Phase 2a portion of the study; update of premedication and instructions; revision of post-infusion monitoring requirements for subjects; update of inclusion and exclusion criteria; closing of cohorts EXP-2, EXP-3, and EXP-4 to recruitment; clarification of the pre-screening and re-screening processes; clarification of the minimum amount of AFM24 to be received by subjects to be eligible to continue in the study; revision of stopping rules; update of AFM24 monitoring to reflect the current safety data for AFM24 administration; clarification of time points of study procedures; update of definition of the full analysis set; addition of PPS; update of the definition of disease control rate; clarification of the approach for the use of interim analyses for the experimental and exploratory cohorts; clarification of mechanism of reporting of AEs and handling of related AEs to authorized auxiliary medicinal products (AxMPs) to ensure consistency across sites; update to the reporting period of Serious AEs; addition of information on personal data breach notification and assessment; update of the EU Regulations from Directive 2001/20/EC to 563/2014; update of subjects privacy information.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

This trial was prematurely discontinued due to the financial situation of the sponsor, and not for safety or efficacy reasons.

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Clinical trials

Clinical Trial Results: A Phase 1/2a Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AFM24 in Combination with Atezolizumab in Patients with Selected Advanced/Metastatic EGFR-expressing Cancers

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1 - Adverse events to be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period (Cycle 1)

Primary: Phase 1 - Adverse events to be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period (Cycle 1)

Primary: Phase 2a - Objective response rate according to RECIST v1.1 determined by Investigator assessment

Primary: Phase 2a - Objective response rate according to RECIST v1.1 determined by Investigator assessment

Secondary: Phase 1 - Objective response rate according to RECIST v1.1 determined by Investigator assessment

Secondary: Phase 1 - Objective response rate according to RECIST v1.1 determined by Investigator assessment

Secondary: Phase 2a - Progression-Free Survival according to RECIST v1.1 by Investigator assessment

Secondary: Phase 2a - Progression-Free Survival according to RECIST v1.1 by Investigator assessment

Secondary: Phase 2a - Duration of Response according to RECIST v1.1 by Investigator assessment

Secondary: Phase 2a - Duration of Response according to RECIST v1.1 by Investigator assessment

Secondary: Phase 2a - Clinical benefit rate according to RECIST v1.1 by Investigator assessment

Secondary: Phase 2a - Clinical benefit rate according to RECIST v1.1 by Investigator assessment

Secondary: Phase 2a - Disease control rate according to RECIST v1.1 by Investigator assessment

Secondary: Phase 2a - Disease control rate according to RECIST v1.1 by Investigator assessment

Secondary: Number of patients with Treatment-Emergent Adverse Events and Serious Adverse Events

Secondary: Number of patients with Treatment-Emergent Adverse Events and Serious Adverse Events

Secondary: Maximum concentration of AFM24 over the dosing interval (Cmax)

Secondary: Maximum concentration of AFM24 over the dosing interval (Cmax)

Secondary: Time to maximum concentration of AFM24 over the dosing interval (Tmax)

Secondary: Time to maximum concentration of AFM24 over the dosing interval (Tmax)

Secondary: Minimum concentration of AFM24 over the dosing interval (Cmin)

Secondary: Minimum concentration of AFM24 over the dosing interval (Cmin)

Secondary: The area under the curve (AUC) of AFM24 from the time of dosing to 168 hours post dose (AUCtau)

Secondary: The area under the curve (AUC) of AFM24 from the time of dosing to 168 hours post dose (AUCtau)

Secondary: Number of patients developing antidrug antibodies against AFM24

Secondary: Number of patients developing antidrug antibodies against AFM24

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 1/2a Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AFM24 in Combination with Atezolizumab in Patients with Selected Advanced/Metastatic EGFR-expressing Cancers